Corticosteroid in dentistry

“DREAM IS NOT WHAT YOU SEE

DURING SLEEP, IT IS WHAT DON’T

LET YOU SLEEP.”

CORTICOSTEROIDS

Presented by:

Dr. Ankit Patel

Contents History

Physiology

- Pituitary gland

- Adrenal gland

Regulation of Cortisol Release

Glucocorticoids and mineralocorticoids

- Pharmacological Actions

Classification of glucocorticoids and mineralocorticoids

Mechanism of Action

Pharmacokinetics

Therapeutic use

Use of corticosteroids in endodontics

Drug interaction

Adverse reactions

Contraindications

Conclusion

References

History

Addison (1849) first appreciated the clinical importance of the adrenal glands

and described fatal outcomes in patients with adrenal destruction during a

presentation to the South London Medical Society.

Brown sequard (1856) demonstrated that bilateral adrenalectomy was fatal in

laboratory animals. It was later shown that the adrenal cortex, rather than the

medulla, was essential for survival in these experiments. Subsequently, Tate

and colleagues isolated and characterized a distinct corticosteroid aldosterone,

that had potent effects on fluid and electrolyte balance (and therefore was

termed mineralocorticoid). During the decades following 1930, there was an

intensive search for the active principles that could account for the essential

role of the adrenal gland.

Reichstein and Von Euw (1937) prepared dexamethasone synthetically and

demonstrated its presence in adrenal glands.

Hench and Co-workers (1949) reported the effectiveness of cortisone and

corticotropin in the treatment of rheumatoid arthritis.

PHYSIOLOGY- PITUITARY

GLAND

PHYSIOLOGY-PITUITARY

GLAND

Adrenal Gland Anatomy

• Small, triangular glands loosely attached to the

superior aspects of the kidneys.

• Divided into two morphologically and distinct

regions

- adrenal cortex (outer)

- adrenal medulla (inner)

Adrenal Cortex

•Hormones produced by the adrenal cortex are referred to

as corticosteroids.

•These comprise mineralocorticoids, glucocorticoids and

androgens.

•The cortex is divided into three regions:

• zona glomerulosa

• zona fasciculata

• zona reticularis

Zona Glomerulosa

Outermost zone – just below the adrenal capsule

Secretes mineralocorticoids.

Mineralocorticoids are aptly termed as they are

involved in regulation of electrolytes in

extracellular fluid.

The naturally synthesized mineralocorticoid of

most importance is aldosterone.

Zona Fasciculata

Middle zone – between the glomerulosa and reticularis

Primary secretion is glucocorticoids.

Glucocorticoids, as the term implies, are involved the

increasing of blood glucose levels. However they have

additional effects in protein and fat metabolism.

The naturally synthesized glucocorticoid of most

importance is cortisol.

Zona Reticularis

Innermost zone – between the fasciculata and medulla

Primary secretion is androgens.

Androgenic hormones exhibit approximately the same effects as the male sex hormone –testosterone.

Regulation of Cortisol Release

• Cortisol release is regulated by ACTH

• Release follows a daily pattern - circadian

• Negative feedback by cortisol inhibits the

secretion of ACTH and Corticotropin releasing

hormone (CRH).

Regulation of Cortisol Release

The important glucocorticoid secreted in human

being is hydrocortisone (10 mg/ day)

Enhanced release can be caused by:

physical trauma

infection

extreme heat and cold

exercise to the point of exhaustion

extreme mental anxiety

Natural Cortisol Aldosterone

Daily secretion 10mg 0.125mg

Conc. in plasma

8 a.m. 16 ug/100ml 0.01 ug/100ml

4p.m. 4 ug/100ml 0.01 ug/100ml

Regulation of Cortisol Release

• 95 % is bound to corticosteroid binding

globulin (CBG or transcortin).

• Free cortisol is only 1 µ gm per 100 ml.

Pharmacological Actions1. Carbohydrate

2. Protein

3. Lipid

4. Electrolyte & water(mineralocorticoid action)

5. CVS

6. Skeletal Muscle

7. CNS

8. Stomach

9. Blood

10. Anti-inflammatory

11. Immunosuppressant

12. Respiratory system

13. Growth & Cell Division

14. Calcium metabolism

Actions: Carbohydrate and protein metabolism

Neoglucogenesis◦ Peripheral actions (mobilize AA & glucose and glycogen)

◦ Hepatic actions

Peripheral utilization of glucose

Glycogen deposition in liver(activation of hepatic glycogen synthase)

Amino acid level

Protein breakdown

- Hyperglycaemia

Permissive role in nature: promote lipolysis due

to glucagon, GH, Adr and throxine.

Redistribution of Fat over neck, face, and

shoulder-moon face, fish mouth, buffalo hump.

Increases sensitivity of adipocytes to insulin.

Actions: Lipid metabolism

Actions: Electrolyte and water balance

Aldosterone is more important

Act on D.T. & C.D. of kidney

◦ Na+ reabsorption

◦ Urinary excretion of K+ and H+

If mineralo-dificency

Results into

se Maximal tubular reabsorption capacity for Na+

Progressively

Na+ lost

So

Kidney absorb water without attendant Na+(to maintain E.C.F. level which nevertheless decreases)

Dilutional hyponateremia

Excess water enters cells

Cellular hydration

Blood volume and hematocrit

Hyperkalemia and acidosis

Circulatory collapse

So

ADRENAL CORTEX ESSENTIAL FOR SURVIVALIf mineralo-excessive

It causes fluid retention and hypertension

Restrict capillary permeability

Maintain tone of arterioles

Mineralocorticoid-induced Na+ retention

ECF

B.P.

Permissive action

α & βreceptors

Vascular reactivity

Actions: Cardiovascular system

Potentiates the pressor response of blood vessels to

the action of catecholamines

On Skeletal muscle has permissive action:

Weakness occur in both cases

Addison’s disease(hypocorticism)

Work capacity, weakness & fatigue

circulation

Addison's disease: weakness & fatigue is due to inadequacy of circulatory system to respond to stress of increased muscular activity.

Primary aldosteronism(hypercorticism)

Weakness

Hypokalemia

Excessive corticoids action causes muscle wasting and myopathy leads to weakness

Actions: Skeletal Muscles

Needed for maintaining the normal function of Skeletal muscle

Direct:

◦ Mood elevation

◦ Behavior –incresead Euphoria, nervousness, irritabilility

◦ Brain excitability

Indirect:

◦ maintain glucose, circulation and electrolyte balance

Actions: CNS ( Central nervous system)

Aggravate peptic ulcer. May be due to

Gastric acid & pepsin secretion

Actions: Stomach

RBC: Hb & RBC content

WBC: Lymphocytes, eosinophils,

monocytes, basophils

Actions: Blood

Recruitment of WBC and monocytes macrophage

into affected area & elaboration of chemotactic

substances

Lipocortin

TNF from phagocytic cells

IL1 from monocyte-macrophage

Formation of Plasminogen Activator

Expression of cyclo-oxygenase II

Actions: Anti-inflammatory

Phospholipids

Arachidonic acids

lipoxygenase Cycylooxygenase

LeukotrieneProstaglandins,

Thromboxane

Prostacyclins

Phospholipase A2

Lipocortin

Corticosteroids

PAF by lipocortin

Anti-inflammatory actions of corticosteroids

Histamine release

Fibroblast proliferation

Extravasation of leukocytes

T-lymphocytes proliferation

Vasoactive & chemoattractive factors

Secretion of lypolytic & proteolytic enzymes

Immunosuppressive & anti-allergic actions

Suppresses all types of hypersensitivity & allergic

phenomenon

At High dose: Interfere with all steps of immunological

response

Causes greater suppression of CMI (graft rejection & delayed

hypersensitivity)

Transplant rejection: Antigen expression from grafted tissues, delay

revascularization, sensitization of T lymphocytes etc.

Inhibit cell division or synthesis of DNA

Delay the process of healing

Retard the growth of children

Actions: Growth & Cell division

Intestinal absorption

Renal excretion

Excessive loss of calcium from spongy bones (e.g.,

vertebrae, ribs etc)

Ca2+ absorption excretion

Total body calcium store

Actions: Calcium metabolism

Not bronchodilators

They reduce the bronchial hyper-reactivity and increase the peak

expiratory flow rate in asthmatic patients.

They are not effective during an acute attack or in status

asthmaticus.

Most potent and most effective anti-inflammatory

Effects not seen immediately (delay 6 or more hrs)

Inhaled corticosteroids are used for long term control

Before birth: Induce surfactant synthesis in fetal lung. Useful in

Respiratory Distress Syndrome

Actions: Respiratory system

Classification of glucocorticoids

and mineralocorticoids

COMPOUND GLUCO MINERALO EQVI. DOSE

G

L

U

C

O

C

O

R

T

I

C

O

I

D

S

SHORT ACTING

t1/2 < 12 hr

INTERMEDIATE

ACTING

t1/2 < 12-36hr

LONG ACTING

t1/2 > 36 hr

1. HYDRO-

CORTISONE

2. CORTISONE

3. PREDNISOLONE

4. METHYL

PREDNISOLONE

5. TRIAMCINOLONE

6. DEXAMETHASONE

7. BETAMETHASONE

1

0.8

4

5

5

25

25

1

0.8

0.8

0.5

0

0

0

20 mg

20mg

5mg

4mg

4mg

0.75mg

0.75mg

M

I

N

E

R

A

L

O

-

C

O

R

T

I

C

O

I

D

S

8. DESOXYCORTICOSTERONE

ACETATE(DOCA)

9. FLUDROCORTISONE

10.ALDOSTERONE

0

10

0.3

100

150

3,000

2.5mg

(sublingual)

0.2mg

Not used

clinically

Mechanism of Action

Mechanism of Action

Most of the established pharmacological effects

of glucocorticoids are mediated by cytoplasmic

glucocorticoid receptors.

After binding to the receptor, the steroid-

receptor complex binds to chromatin and

stimulate the formation of mRNA.

The mRNA stimulates the synthesis of enzymes

which produce various pharmacological actions.

Pharmacokinetics

ABSORPTION

Can be given by oral, parenteral and topical route.

Oral bioavailability of synthetic corticosteroids is high.

Hydrocortisone after oral administration undergoes extensive first pass metabolism in liver. So preferd route is parenteral.

Systemic absorption is by Topical/local e.g. Skin, synovial space, conjuctiva, intranasal, enema, inhalation.

DISTRIBUTION

90% bound to plasma protein, mostly to a specific corticosteroid binding globulin(globulinor Transcortin) and albumin.

METABOLISM: By reduction or conjugation

REDUCTION

4,5 bond,3ketone tetrahydrocortisol

( liver)

CONJUGATION

Sulfate or glucuronide (liver & kidney)

Excreted in urine

The synthetic derivatives are metabolised slowly and have longer duration of action.

Therapeutic uses:Endocrine Disorders• Replacement therapy

Acute adrenal insufficency: (emergency)

Hydrocortisone(100 mg IV q 6-8 h)/dexamethasone(4-10 mg IV q 6-8 h.)are given IV first as bolus injection and then infusion with NS and glucose solution. Inj.Hydrocortisone 100 mg every 4-6 hrs, Tab.Hydrocortisone 20mg in the morning, Tab.Hydrocortisone 10 mg in the evening, I.V. fluid.

Chronic adrenal insufficiency (addison’s disease)

Hydrocortisone given orally along with adequate salt and water allowance. Few pt. require mineralocorticoid: fludrocortisone/DOCA. Tab.Hydrocortisone 20mg in the morning, Tab.Hydrocortisone 10 mg in the evening, Fludrocortisone 0.05 to 0.2 mg/day oral.

Congenital adrenal hyperplasia (adrenogenital syndrome)

◦ Deficiency of steroidogenic enzymes mostly 21-hydroxylase. As a result synthesis of hydrocortisone and aldosterone suffers.

◦ Hydrocortisone 0.6mg/kg daily for suppression of pituitary.

◦ If salt wasting persists-fludrocortisone 10-20ug/kg daily.

Pharmacotherapy for nonendocrine diseases

General principles must be observed

1. Single dose (even excessive) is not harmful: can be used to

tide over mortal crisis even when benefits is not certain.

2. Short courses (even high doses) are not likely to be

harmful in the absence of contraindications: starting dose

can be high in severe illness.

3. Long term usesis potentially hazardous: keep the dose

minimum, which is found by trial and error; even partial

relief may have to be tolerated.

4. No abrupt withdrawal after a corticoids has been given >2-

3 weeks: may precipitate adrenal insufficiency.

5. Infection, severe trauma or any stress during corticoid

therapy-increase the dose.

Arthrides:

Rheumatic arthritis-Oral Prednisolone (5 to 10mg)/day, IA Triamcinolone acetonide 5-20mg

Osteoarthritis- IA Triamcinolone acetonide 5-20mg

Rheumatic fever

Gout

Collagen diseases: SLE, polyarthrits nodosa, dermatomyosotis, nephroticsyndrome, glomerulonephritis and related diseases need corticosteroids may be life saving. Prednisolone 1mg/Kg start; gradually reduce the dose

Severe allergic reactions

Autoimmune diseases: autoimmune hemolytic anaemia, thrombocytopenia, active hepatitis respond to corticoids. Its also in severe cases of myasthenia gravis along with neostigmine.

Bronchial asthma: used either for-status asthmaticus, severe chronic asthma. Nowadays corticoids are used for mid asthma and short couses of oral steroids may be used to tide over acute excerbations.

Other lung diseases: corticoids benefits aspiration pneumonia and

pulmonary oedema from drowning. Given during late pregnancy corticoids

accelerate lung maturation in the foetus and prevent respiratory distress

syndrome at birth. Such therapy may be undertaken if premature delivery

is contemplated.

Infective diseases: indicated in serious infection to tideover crisis to prevent

complications. They are indicated in conditions like severe forms of TB,

severe lepra reaction, certain forms of bacterial meningitis and

pneumocystis carinii pneumonia with hypoxia in AIDS

Eye diseases-diseases-Outer eye & anterior segment: local application,

Posterior segment: systemic use, Caution: bacterial, viral & fungal

conjunctivitis.

Skin diseases-Pemphigus: Life saving therapy is steroids. Eczema,

dermatitis & psoriasis: respond well

Intestinal diseases

Cerebral oedema-Questionable value in cerebral edema following trauma, cerebrovascular edema. Valuable in edema associated with neoplasm and parasites

Malignancies-Part of multi drug regimens for acute lymphatic leukaemia (children), chronic lymphatic leukaemia (adult).

Open transplantation and skin allograft

Shock: IV corticoids are given as a desperate measure in septicaemic shock.

To test adrenal-pituitary axis function: dexamethasone suppresses adrenal-pituitary axis at doses which do not contribute to steroid metabolites in urine-responsiveness of the axis can be tested by measuring daily urine steroid metabolite excretion.

Organ transplantation

Bell’s palsy

Thrombocytopenia

Myasthenia gravis

Spinal cord injury

Sarcoidosis

Non-endocrine diseases

- Miscellaneous

Use in endodontics

Corticosteroids in dentistry,are used primarily to decrease post-operative edema and manage oral inflammatory diseases.

Post treatment flare-ups after endodontic treatment can be attributed to the inflammation,infection or both in periradicular tissues.

Glucocorticosteroids are known to reduce the acute inflammatory response by suppressing vasodilatation,migration of PMN’s leukocytes,andphagocytosis.

Intracanal placement with 2.5% steroid and saline---study conducted—resulted in significant reduction of incidence of post-operative pain in teeth with vital pulp

Other study with Ledermix,Formocresol,or calcium hydroxide as intracanal medicament resulted in steroid showing significant effects in reducing post-operative pain.

Ledermix: Schroeder developed the material

Triamcinolone Acetonide and Demethylchlortetracycline

30% triamcinilone is released in first 24 hrs and remaining 70% over a period of 14 weeks

Available as 2 forms

1.Water soluble ‘cream’

2. Rapidly hardening ‘cement’

46

A. Open-cavity pulpitis

47

B: Closed-cavity pulpitis

48

Krasner P, Jackson E (1986)reported the use of orally

administered dexamethasone alone for the management

of pain following routine endodontic instrumentation.

Fachin EVF, Zaki AE (1991) conducted a study to

histologically investigate steroid effects on the dental

pulp. The results showed that topical application of

corticosteroids as an intracanal medicament reduced

inflammatory changes in the pulp as compared with

controls.

Erisen R, Yucel T, Kucukay S et al (1989) reported a

case of hypoesthesia caused by endomethasone

overflowing into the mandibular canal. Endomethasone

contains hydrocortisone, which can contribute to its

toxicity.

USES IN ORAL MEDICINE

Lichen planus

Oral submucous fibrosis

Aphthous stomatitis

Pemphigus

Bell’s palsy

Mucocele

Psoriasis

Erythema multiforme

Herpes virus infection

Central giant cell granuloma

Temporomandibular joint pain and dysfunction

Chronic ulcerative stomatitis

Pystomatitis vegetans

Giant haemangioma

Meischer’s granulomatous cheilitis

USES IN ORAL SURGERY :

Third molar surgery

Reconstructive oral surgery

Preprosthetic surgery

Drug interaction

Adverse reactions

Minerlocorticoid: sodium and water retention, edema, hypokalemia alkalosis

and a progrssive rise in BP(rarely).

Glucocorticoid

Cushing’s disease

Fragile skin, purple striae

Hyperglycaemia

Muscular weakness

Susceptibility to infection

Delayed wound healing

Peptic ulceration

Osteoporosis

Posterior subcapsular cataract

Glaucoma

Growth retardation

Fetal abnormalities

Psychiatric disturbances

Suppression of HPA axis

Contraindications

Infections

Hypertension with CCF

Psychosis

Peptic ulcer

Diabetes mellitus

Osteoporosis

Glaucoma

Pregnancy : (prednisolone preferred)

TB

Epilepsy

Renal failure

Precautions during therapy

Following examinations of the patient to be

done before, during and after steroid therapy

Body weight

X-ray of spine

Blood glucose

Examination of the eye

B.P.

TOPICAL CORTICOSTEROIDS

Examples of topical corticosteroids

include:Betamethasone dipropionate (diprosone),

Fluocinolone acetonide (flurosyn), Hydrocortisone (cort-

dome), Triamcinolone acetate (Aristocort).

ACTIONS AND USES

Topical corticosteroids exert localized anti-inflammatory

activity.

When applied to inflamed skin, they reduce itching,

redness, and swelling.

These drugs are useful in treating skin disorders, such as

psoriasis, dermatitis, rashes, eczema, insect bite

reactions, and first and second-degree burns, including

sunburns.

Adverse reactions

Localized reactions may include burning,

itching, irritation, redness, dryness of the

skin, and secondary infection.

CONTRAINDICATIONS, PRECAUTIONS,

AND INTERACTIONS

The topical corticosteroids are contraindicated

in patients with known hypersensitivity to the

drug and for ophthalmic use (may cause steroid-

induced glaucoma or cataracts).

The topical corticosteroids are used cautiously

during pregnancy and lactation.

There are no significant interactions when

administered as directed.

Conclusion

No doubt these are called as wonder drugs or

magic drugs which are used in life threatning

conditions can cost the life when not used

properly.

References

Pharmacology and Pharmacotherapeutics-

R.S. Satoskar

Textbook of pharmacology- K.D. Thripati.

Pharmacology for dentistry-Dr Surendra

Singh

Introductory Clinical Pharmacology- Roach